Effects of ketoconazole on the iodide uptake by FRTL-5 cells.

Ketoconazole is an imidazole derivative used as an antimycotic agent with reported effects on the endocrine system, but very little is known about its possible actions on thyroid function. Our purpose was to study the influence of this substance on the basal and TSH-stimulated iodide uptake in the rat thyroid cell strain FRTL-5. Ketoconazole (1-50 mumol/l) was shown to slightly increase the basal iodide uptake but, at higher concentrations (75-100 mumol/l), it sharply decreased iodide uptake below the basal levels. When the cells were cultured under bTSH stimulation (30 UI/l), the inhibitory effect of ketoconazole was exerted at concentrations as low as 25 mumol/l. This inhibition was observed even if it was added to the culture medium immediately before the Na125I addition. Forskolin, a stimulator of adenylate cyclase activity, was unable to prevent the iodide uptake inhibition. Low doses of ketoconazole increased cAMP concentrations. In the presence of TSH this effect was more evident in an inverse dose-dependent way. Because of its dual action, it can be assumed that ketoconazole could influence the iodide uptake in the FRTL-5 cells through more than one mechanism.

Graves' disease: evolution and prognosis after eight months of treatment with methimazole.

We studied 26 patients with Graves' disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1% of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60% and a specificity of 100%. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse.

Graves disease: evolution and prognosis after eight months of treatment with methimazole.

We studied 26 patients with Graves disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1

of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60

and a specificity of 100

. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse.

Graves disease: evolution and prognosis after eight months of treatment with methimazole.

We studied 26 patients with Graves disease, from a population with sufficient iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their prognosis. The patients were followed during 12-60 months, and blood samples were collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with T3/T4 index and TRAb significantly higher than those under remission. The T3/T4 index correlated with TRAb. All the TRAb-positive patients, and only 57.1

of the negatives, relapsed. The relapses were significantly more frequent prior to the 6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who relapsed during that period, showed TRAb and age means significantly higher than those under remission. The TRAb test, as a prognostic marker of evolution, showed a sensitivity of 60

and a specificity of 100

. No significant differences were found between evolution to relapse or to remission and the other parameters. It can be concluded that TRAb and T3/T4 index were different in the group that relapsed from that which remitted, and that a TRAb positive value, at the moment of treatment withdrawal, is a useful marker of relapse.

Changes in calcitonin release during sympathetic nerve degeneration after superior cervical ganglionectomy of rats.

To assess the role of peripheral sympathetic nerves in the regulation of calcitonin release, rats subjected to superior cervical ganglionectomy (SCGx) 16-28 h earlier were used. The time periods selected allowed us to examine C cell response during the supraliminal release of sympathetic transmitter that accompanies anterograde degeneration of nerve varicosities as well as during the neural paralysis that ensues thereafter. At the time intervals examined, SCGx did not result in significant changes of basal serum calcitonin or Ca levels. The intraperitoneal administration of CaCl2 brought about an impending increase of serum Ca to the same extent in SCGx and sham-operated rats. A significant depression of calcitonin release was observed in rats killed around the time of nerve terminal degeneration (16-21 h post SCGx) but not about 10 h later. Additionally a delay to achieve a maximal calcitonin response was apparent during nerve degeneration. Injection of the alpha-adrenoceptor blocker phenoxybenzamine significantly increased basal calcitonin levels and restored the depressed calcitonin response to hypercalcemia seen in SCGx rats. Treatment with the beta-adrenoceptor-blocker propranolol counteracted phenoxybenzamine activity but was unable to modify per se calcitonin release in SCGx or sham-operated rats. Basal Ca levels and their increase after intraperitoneal CaCl2 were similar in all examined groups regardless of the drug injected. In an additional experiment phenoxybenzamine injected into SCGx rats in doses one-fifth those employed earlier still reversed both the depression in maximal calcitonin response as well as the delay to attain maximal release after CaCl2, but was unable to affect basal calcitonin levels.(ABSTRACT TRUNCATED AT 250 WORDS)